Review Article ISSN 2250-0480 Vol 2/Issue 1/Jan-Mar 2012 L-13 Pharmaceutical Science Biotechnology EPIGENETIC CHANGES AND THEIR REVERSAL IN CANCER ABHIMANYU KUMAR JHA 1* , MEENAKSHI JHA 2 , VINAY DWIVEDI 1 , RASHMI CHANDRA 1 ,VIVEK KUMAR 1 , JAGDEEP KAUR 2 1-Department of Biotechnology, IMS Engineering College, Ghaziabad (Uttar Pradesh), INDIA 2-Department of Biotechnology, Panjab University, Chandigarh, INDIA ABSTRACT Cancer is caused by genetic as well as epigenetic changes. Chemotherapy is considered the mainstay of cancer therapy. But multiple side effects of chemotherapy has created a demand for developing other novel and specific targets for cancer therapy. The potential reversibility of epigenetic changes have resulted in the reactivation of epigenetically silenced tumor suppressor genes being an emerging strategy for the treatment of cancer. Epigenetic modifiers like DNA methyltransferase (DNMT) inhibitors and histone deacteylase (HDAC) inhibitors induce the re-expression of epigenetically silenced genes in vitro and in vivo. Moreover, they demonstrate safety and efficacy against neoplastic diseases in clinical trials. DNMT inhibitors like 5-azacytidine and 5-aza-2’-deoxycytidine have recently been approved by FDA for the treatment of myelodysplastic syndrome. Still the mechanism of action behind their clinical efficacy remains unclear. In this review, the different epigenetic changes taking place during tumor progression and their reversal has been discussed. Key words: chemotherapy, DNMT, HDAC, epigenetic modifiers, INTRODUCTION The genetic basis of cancer as a disease is well established. However, the involvement of factors other than changes in nuclear DNA sequence in cancer development and progression gained much attention in the last thirty years. Epigenetics refers to heritable reversible changes in gene expression that occur without any changes in the DNA sequence. Epigenetic modifications affect the nuclear DNA and/or the nucleosomes-incorporated histones and consequently modify gene expression. Ongoing clinical trials intend to identify tumor suppressor genes that upon re-expression can induce remission and cure in patients. The DNA methyltransferase (DNMT) inhibitors azacitidine and decitabine are among the new agents approved by the FDA for the treatment of myelodysplastic syndrome (MDS). In this review, various epigenetic changes, like histone modificationsthe development of different DNMT inhibitors as epigenetic modifiers for the treatment of cancer are discussed. HISTONE MODIFICATIONS The posttranslational modifications of the amino terminal tail of histones like methylation, acetylation, phosphorylation, ubiquitination and SUMOylation can directly affect the packing of nucleosomes and chromatin architecture (Shilatifard A, 2008; Jones PA and Baylin SB, 2002; Weake VM and Workman JL, 2008). In accordance with this, the histone code hypothesis (Paro R, 2000; Turner BM, 2000) proposes a combinatorial code of histone modifications that complement the information stored in the DNA sequence and mediate downstream events. Despite the diversity of